TOPLINE:

Efruxifermin significantly reduced both overall fibrosis and septal area in adults with metabolic dysfunction-associated steatohepatitis (MASH) and compensated cirrhosis, based on a post hoc analysis using AI-based digital pathology of data from the phase 2b SYMMETRY study.

METHODOLOGY:

• The original trial included 181 participants with MASH and compensated cirrhosis who received weekly subcutaneous efruxifermin (28 mg or 50 mg) or placebo. As previously reported by Medscape Medical News, the initial results found that a 50-mg dose of efruxifermin once daily significantly improved overall fibrosis, as per conventional pathology, at 96 weeks compared to placebo.
• The current analysis looked at septa area and cardinal features of cirrhosis as well as fibrosis in 130 patients for whom unstained liver biopsies were available at baseline, and at 36 and 96 weeks.
• Biopsies were imaged using second harmonic generation/two-photon excitation fluorescence microscopy and then analyzed with the qSepta and qFibrosis AI-based digital pathology algorithms.
• The final analysis included 40 patients treated with 28 mg efruxifermin, 40 treated with 50 mg efruxifermin, and 44 who received placebo.

TAKEAWAY:

• At 96 weeks, significantly more patients in the 50-mg efruxifermin group had improvement in fibrosis by at least one stage vs those treated with placebo (46% vs 25%, P < .05), consistent with the results from conventional pathology.
• The reduction in median septa area was significantly greater at week 96 in both the 28-mg and 50-mg efruxifermin groups than in the placebo group (-35% and -36% vs -10%, P < .05 for both).
• Overall, more patients in both efruxifermin groups showed decreased septa area, while more placebo patients showed an increased septa area.
• Median septa area changes ranged from -34% to -42% across the treatment groups of patients who responded to efruxifermin with fibrosis improvement.
• Septa area was also reduced in NASH CRN fibrosis nonresponders treated with efruxifermin but not with placebo.

IN PRACTICE:

“Efruxifermin reduced septa area, which was associated with disease severity, independent of categorical histological fibrosis response,” the authors wrote in their abstract.

“Digital analysis of septal area, which may detect more subtle changes in fibrosis, demonstrated a broad antifibrotic effect…that may yield clinically meaningful improvements in liver outcomes,” they concluded.

SOURCE:

The study was presented by Mary Rinella, MD, professor of medicine in the Gastroenterology, Hepatology, and Nutrition section at the University of Chicago, Chicago, at The Liver Meeting 2025: American Association for the Study of Liver Diseases (AASLD). 

LIMITATIONS:

The researchers noted that the findings were limited by the small study population. 

DISCLOSURES:

The study was funded by Akero Therapeutics.

Rinella disclosed serving as a consultant for multiple companies including Akero.